The present disclosure relates to a process for the purification of anhydrosugar alcohols by distillation and/or recrystallization in the presence of an aliphatic alcohol, and the products of the purification, which are desirably greater than 99.0% pure and, even upon thermal treatment, are substantially colorless.
Anhydrosugar alcohols, in particular derivatives of mannitol, iditol, and sorbitol, are known for their therapeutic uses and uses in food. Further, at least isosorbide, 1,4:3,6-dianhydrosorbitol, is being examined as a renewable natural resource for the manufacture of polymers, especially polyesters, because isosorbide is a derivative of sorbitol, which can be derived from various natural resources, including corn starch and cassava (tapioca). See related applications on processes of making and products made from polymers having isosorbide, terephthaloyl and ethylene glycol moieties, U.S. patent applications Ser. Nos. 09/064,844; 09/064,950; 09/064,846; 09/064,858; 09/064,826; 09/064,719; 09/064,862; and 09/064,720, all filed Apr. 23, 1998, each of which are incorporated in their entirety by reference.
The purity requirements for the use of anhydrosugar alcohols differ depending upon the intended application. In food and drug applications, for example, one requirement is that there be no impurities that cause harm to the individual or organism using the material containing the anhydrosugar alcohol. By this definition, an anhydosugar alcohol may contain numerous other materials or impurities that are not anhydrosugar alcohols and yet still be considered pure for a food or drug application. In polymer applications, especially those that require optical clarity, such as polymers used in packaging, one monomer purity requirement is that there not be any materials or impurities present in the monomer that could cause the resultant polymer to develop an unacceptable degree of color during synthesis and/or processing. Impurities that may be permissible in anhydrosugar alcohols used for food and drug applications may not in fact be acceptable for anhydrosugar alcohols that are to be used in polymer applications because those impurities may lead to the development of an unacceptable level of color during the synthesis or processing of the polymer.
Several methods of purifying anhydrosugar alcohols are known in the art. For example, such alcohols can be purified by vacuum distillation or recrystallization from an organic solvent such as ethyl acetate and/or ether, as disclosed in Flxc3xa8che and Huchette, xe2x80x9cIsosorbide: Preparation, Properties and Chemistry,xe2x80x9d starch/stxc3xa4rke 38 (1986) Nr. 1, pp. 26-30 at 29, or methyl ethyl. ketone as disclosed in U.S. Pat. No. 3,454,603. However, these methods do not sufficiently remove impurities that may lead to the development of an unacceptable level of color during polymer synthesis and/or processing.
Purification by recrystallization from water is also known, as disclosed in Beck, xe2x80x9cDianhydrosorbitolxe2x80x94a new pharmaceutical ingredient,xe2x80x9d Pharmaceutical Manufacturing International, p.97-100 at 97-98 (1996), although the product resulting from this is only about 97% pure. Generally, water is undesirable as a solvent because anhydrosugars are extremely hygroscopic.
Purification by distillation under reduced pressure in the presence of borohydride ions has also been proposed, as disclosed by Flxc3xa8che and Huchette, p. 29, and as described in U.S. Pat. No. 3,160,641 for the reduction of periodate-consuming impurities in isosorbide using boric acid.
Methods are also known for the purification of anhydrosugar alcohol derivatives, and for purification of anhydrosugar alcohol precursors. Purification of specific anhydrosugar alcohol derivatives by recrystallization from methanol and ethanol is demonstrated in, for example, Hockett et al. J. Am. Chem. Soc., Vol. 68, p.930-935 (1946); Copeand Shen, J. Am. Chem. Soc. p.3177-3182 (1956); and Ojrzanowski et al., Acta Pol. Pharm. 43(6) p.567-71 (1986).
Further, purification of precursors such as D-mannitol and D-glucitol by extraction or recrystallization from ethanol or a mixture of ethanol and water, respectively, are demonstrated by Block et al. in Acta Chem. Scan. (43) p.264-268 (1989).
The use of methanol and ethanol in the recrystallization of precursors and derivatives of anhydrosugar alcohols is also demonstrated by Defaye et al., Carb. Res. 205 p.191-202 (1990). Defaye et al. also demonstrates recrystallization of A dianhydrosugar alcohols, specifically, 1,4:3,6-dianhydro-D-mannitol and 1,4:3,6-dianbydro-D-glucitol. However, these recrystallizations do not use aliphatic alcohols such as methanol, ethanol or ethylene glycol as solvents.
A method of purification of monoanhydrohexitols and dianhydrohexitols is also set forth in U.S. Pat. No. 4,564,692 to Feldmann et al. However, this process requires placing the anhydrosugar alcohol in a heavy liquid having 1-20% water by weight and adding seed crystals of the desired anhydrosugar alcohol to be recrystallized.
There is no known teaching of purifying an anhydrosugar alcohol by recrystallization from aliphatic alcohols such as methanol, ethanol or ethylene glycol. The above processes, as known in the art, are directed to purification of the anhydrosugar alcohol for use in food or pharmaceutical compositions. The inventors herein are unaware of any previous purification process achieving the required level of purity for use in polymers.
In view of the above, a simple and cost effective method of purifying anhydrosugar alcohols, resulting in an extremely pure product, is desired. Further, an extremely pure anhydrosugar alcohol is desired, particularly for use in polymer formation.
The inventors of the present disclosure have discovered that recrystallization from lower aliphatic alcohols, such as methanol and ethanol, as well as melt recrystallization, improves the purity and clarity of color of anhydrosugar alcohols. Distillation also improves the purity of the end product, and may optionally be done over sodium borohydride (NaBH4) or other hydride ion containing compounds. A combination of distillation and solvent or melt recrystallization markedly improves the purity of the end product. Similarly, multiple distillations and/or multiple recrystallizations from lower aliphatic alcohols have been found to markedly increase the purity of the anhydrosugar alcohol.
Further, it is disclosed herein that the purity of the anhydrosugar alcohols is best measured with regard to the relative color of the anhydrosugar alcohol and its ultraviolet (LN) transmittance. A method for obtaining such measurements is herein disclosed.
Also, a method of determining the quality of polymers prepared with the purified anhydrosugar alcohol is disclosed, wherein the anhydrosugar alcohol is annealed at temperatures approaching those used in polymer formation, thereby testing the development of color in the annealed anhydrosugar alcohol at the elevated temperatures necessary for the formation of polymers. The coloring of the resultant annealed anhydrosugar alcohol is indicative of the color that may develop during synthesis and/or processing of the resultant polymer.
Further, use of the purified anhydrosugar alcohols resulting from the above methods in the formation of polymers and products formed therefrom is described.
The process of the invention provides for the purification of anhydrosugar alcohols, whether starting with a commercially available product, or working with a product derived directly from a batch or continuous process for formation of anhydrosugar alcohols.
In the process of the invention, the anhydrosugar alcohol is purified by distillation and/or recrystallization from lower aliphatic alcohols. By xe2x80x9clower aliphatic alcoholsxe2x80x9d it is meant linear aliphatic alcohols, preferably having 1-4 carbons. Most desirably, the alcohols are methanol, ethanol or ethylene glycol. The resulting purified anhydrosugar alcohol is at least 99.0% pure, or free from contaminants, and is preferably colorless.
The anhydrosugar alcohols of the invention are monoanhydro- or dianhydrosugar alcohols. Desirable dianhydrosugar alcohols include isosorbide, isomannide and isoidide. Preferably, the anhydrosugar alcohol of the invention is isosorbide.
Distillation of anhydrosugar alcohols can be performed with or without hydride ion containing compounds, such as borohydride ion containing compounds like NaBH4, or lithium aluminum hydride. In a preferred embodiment, distillation occurs by placing the anhydrosugar alcohol in a flask and subjecting the flask to vacuum distillation at a temperature of at least 60xc2x0 C., preferably at least 70xc2x0 C., most preferably at least 80xc2x0 C. The anhydrosugar alcohol is kept at this temperature until the distillation of all volatile impurities is complete. The flask is then preferably purged with a non-reactive gas, such as nitrogen or argon. A hydride ion containing compound, preferably a borohydride ion containing compound, most preferably NaBH4, may optionally be added to the anhydrosugar alcohol in the flask at this time. The flask is then heated to a temperature of at least 100xc2x0 C., preferably at least 120xc2x0 C., most preferably at least 140xc2x0 C., before evacuation to approximately 1 mbar pressure under vacuum and subsequent distillation. The anhydrosugar is then distilled in vacuo. Preferably, the distillation is performed in an apparatus equipped with a short distillation column. The distilled anhydrosugar alcohol is preferably further purified by one or more additional distillations and/or recrystallizations.
For recrystallization from solution according to the invention herein, the. anhydrosugar alcohol may be placed in a solution of aliphatic alcohols, preferably methanol, ethanol or ethylene glycol. The temperature of the solution is lowered to less than 30xc2x0 C., preferably less than 10xc2x0 C., more preferably less than 0xc2x0 C., and most preferably less than xe2x88x9210xc2x0 C., until recrystallization is complete, usually a period of at least 4 hours. The resultant crystals are collected by filtration and washed with the cold aliphatic alcohol, preferably at or below the temperature of crystallization so as not to dissolve the crystals. The crystals may optionally be dried in vacuo at room temperature. Further recrystallizations from aliphatic alcohols and/or distillations may be performed.
Alternatively, melt recrystallizations of the anhydrosugar alcohol may be performed. Melt recrystallization may be done by any means known in the art and may be performed before or after distillation, or in place of distillation and recrystallization from solution. Typically, melt recrystallization entails heating a compound in the absence of solvent just beyond its melting point, then slowly cooling the molten compound to cause formation of purified crystals of the compound. The purities generally form a liquid surrounding the purified crystals and have a lower melting point than the crystals.
The anhydrosugar alcohol obtained by the above described methods has a purity of at least 99.0%, preferably at least 99.5%, and most preferably at least 99.8%. This level of purity is desirably obtained by no more than three distillations, three recrystallizations from aliphatic alcohol, three melt recrystallizations, or a combination of no more than three of the above described purification methods.
The above methods of purifying the anhydrosugar alcohol may be applied to a batch process. They are also applicable to a continuous process of manufacturing anhydrosugar alcohols with modification as known to one of ordinary skill in the art, as discussed in the copending application, filed this same day herewith, titled CONTINUOUS PROCESS FOR THE PRODUCTION OF ANHYDROSUGAR ALCOHOLS, which is incorporated herein in its entirety.
The formation of anhydrosugar alcohols isolated from a continuous process is driven by the reaction mechanisms of the continuous process. Therefore, yield may be somewhat lower in a continuous process purification than if the purification step were optimized as a separate reaction, or in a batch process. In particular, distillation and/or recrystallization from a continuous process begins with separation of the anhydrosugar alcohol from the solvent of the continuous process. This can, for example, be achieved by direct recrystallization of the anhydrosugar alcohol from the solvent used in the continuous process. Thus, the anhydrosugar alcohol is obtained as a solid. Another means of separating the anhydrosugar alcohol from the solvent of the continuous process is liquid-liquid extraction using water or an aliphatic alcohol such as methanol, ethanol or ethylene glycol. The anhydrosugar alcohol is thus obtained as a solution in water, methanol, ethanol or ethylene glycol. The separated anhydrosugar alcohol is then further purified as discussed above, by distillation and/or recrystallization. This leads to a reaction product with superior purity compared to other processes, and provides a more economical process for the formation of purified anhydrosugar alcohols.
The purity of the anhydrosugar alcohol obtained by distillation and/or recrystallization can be measured by conventional means such as differential scanning calorimetry (DSC), wherein the measurements are taken in accordance with ASTM E 928-96. However, a simpler and very accurate measure of the purity of the anhydrosugar alcohol for use in polymer applications requiring optical clarity can be made by examining the color of the anhydrosugar alcohols, preferably as a supercooled melt. Color determination of an anhydrosugar alcohol may be made by comparison of the anhydrosugar alcohol to any known color system.
For example, one such color system is known as the HSB system, in which colors are determined by assigning values that relate to hue, saturation, and brightness. In this system, hue, typically denoted by the symbol H, has values between 0 and 360, with 0 and 360 being identical. For example, reds have values around 0 (or 360), yellows have values of around 60, and so on through the rest of the color spectrum (green, blue, purple, etc,). Combinations of colors, such as orange (red and yellow), have values between the two numbers, for example, between 0 and 60 for orange. Saturation, typically denoted by the symbol S, indicates the intensity of color, and ranges from 0 to 100, with zero being no intensity, indicating a white color. Brightness, denoted by the symbol B, ranges from 0 for black to 100 for white. In the application of this color system to the rating of monomer or polymer color, saturation (S) values close to 0 and brightness (B) values close to 100 are desirable. At a saturation value of zero, hue has no meaning.
For best results, it is preferred to compare the discoloration of supercooled melts of the anhydrosugar alcohol at room temperature. This eliminates color differences which may be caused by the effect of the particle size of a solid. For example, use of crystals or fragments of anhydrosugar alcohol could produce different colors based on sample and particle size due to the amount of light refraction in, or reflection from, the sample. Further, it is desirable to evaluate the color of the anhydrosugar alcohol after it has been subjected to a temperature history similar to that used in polymer synthesis and/or processing in order to determine its usefulness for incorporation in polymers. Therefore, it is preferred that a sample of purified anhydrosugar alcohol be annealed in a clear glass tube at a temperature of at least 260xc2x0 C., preferably 285xc2x0 C., for at least four hours, preferably at least eight, then cooled to give a supercooled melt. The annealed anhydrosugar alcohol melt is then compared to a known color chart. The closer the anhydrosugar alcohol is to colorless, the more pure it is.
Alternately, the purified anhydrosugar alcohol can be examined by wavelength transmittance using UV/vis spectroscopy. The wavelength transmittance of the anhydrosugar alcohol is indicative of its coloration, which is at least partially dependent on impurities in the anhydrosugar alcohol. The wavelength transmittance of the anhydrosugar alcohol is determined by UV/vis spectroscopy at specified wavelengths. Because anhydrosugar alcohols are preferably maintained in a crystalline state after purification, spectroscopic measurement is made of anhydrosugar alcohol in a 20% solution of distilled water. The purified anhydrosugar alcohol desirably has UV transmittances when measured in 5 cm cells in a 20% solution of greater than 50% at 224 nm, greater than 65% at 242 nm, greater than 75% at 276 nm, and greater than 85% at 400 nm. Preferably, the percent transmittance is as high as possible.
Color determinations and UV/vis spectroscopy may also be determined on polymers incorporating the purified anhydrosugar alcohol. Whether the purified anhydrosugar alcohol or a polymer incorporating it is examined, the color test is preferred to UV/vis spectroscopy because the examination of the color of the sample utilizes all wavelengths of visible light, thereby providing the full color of the sample as seen by the naked eye. Individual wavelength measurements are not indicative of the total color of the sample, and can be misleading.
By the methods described herein, an anhydrosugar alcohol which is essentially colorless and having a purity of at least 99.0% may be obtained. Preferably, the purity is at least 99.5%, most preferably at least 99.8%. A determination of purity may be made by color determination or UV/vis spectroscopy, as well as other methods known in the art.
The purified anhydrosugar alcohols may be incorporated into polymers, particularly for use in optical grade polymers. For example, a polyester may be formed from an anhydrosugar alcohol, an aliphatic diol such as ethylene glycol and a dicarboxylic acid such as a terephthaloyl moiety, or a dimethyl ester derivative thereof, as demonstrated in applications Ser. Nos. 09/064,844, 09/064,826 and 09/064,720, all filed Apr. 23, 1998, which are each incorporated herein in their entirety by reference. Such polyesters may be used to form commercial products, such as fibers, sheets, films, containers and optical disks, as demonstrated in applications Ser. Nos. 09/064,950, 09/064,846, 09/064,858, 09/064,719 and 09/064,862, all filed Apr. 23, 1998, which are each incorporated in their entirety by reference. In particular, polymers incorporating the anhydrosugar alcohols produced by the process described herein may be formed by polycondensation of the anhydrosugar alcohol with multi-functional containng materials such as polycarboxylic monomers, polycarboxylic acid halides such as acid chloride, polycarbonate monomers such as diphenylcarbonate or phosgene, isocyanates such as toluene diisocyanate and methylene diphenylisocyanate, and dicarboxylic acids, such as terephthaloyl moieties, or dimethyl esters thereof and, optionally, aliphatic diols, such as ethylene glycol.
Examples of the invention described herein are set forth below. These examples are illustrative only and do not encompass the entire scope of the invention, which includes equivalent means and materials as known to one of ordinary skill in the art and as further defined by the disclosure herein and the following claims.
References cited herein are incorporated in their entirety.